Bones not only have an ability of supporting the body but also function as the largest storage-organ of the calcium in the organism and 99% of the calcium present in the organism is accumulated in the bones. In addition, bones are always remodelled through opposite actions of bone resorption and bone formation. This plays an important role on the maintenance of homeostasis of serum calcium. It is known that the activation of osteoclasts which bear an important role in bone resorption causes excessive flow of calcium into blood from bones to break the homeostasis of calcium in blood and induces hypercalcemia. Hypercalcemia is a disease which occurs due to osteectopia of tumor and the number of patients who suffer from it is expected to increase so that development of a treating agent is desired to be created in a hurry. At present, calcitonin, its derivatives, and bisphosphonate derivatives are used as such hypercalcemia treating agents. However, their therapeutic effect is not satisfactory and development of novel drugs replacing them is desired.
On the other hand, it has been reported that osteoclastogenesis inhibitory factor (OCIF) (WO96/26217) known as a protein inhibiting differentiation of osteoclasts has a hypocalcemic action [Biochemical and Biophysical Research Communications, Vol. 245, pp382-387 (1998); Endocrinology, Vol. 139, pp4012-4015 (1998)]. OCIF is expected as a quite new agent treating hypercalcemia. However, since it is a protein, OCIF is metabolized rapidly in the organism. Accordingly, development of an OCIF-preparation which is safer and has more enhanced action has been desired.